Proteoglycan, a major constituent of cartilage matrix, has been shown to be comprised of proteoglycan subunits, core proteins with covalently linked glycosaminoglycan side chains, which are linked non-covalently by hyaluronic acid and link proteins forming huge aggregates. Our recent work has indicated that cartilage proteoglycan has two antigenic components, the core protein of the proteoglycan subunit and the link proteins, which share at least three antigenic determinants. Our objectives are to characterize these antigenic determinants in terms of the primary structure of the proteoglycan molecule and to prepare mono-specific antisera with which to study the distribution of proteoglycan components in cartilage and other connective tissues by immunofluorescence, to better visualize proteoglycan structure by electron microscopy, and to study proteoglycan biosynthesis. The structural and dynamic properties of cartilage and its components are being studied by C13 nuclear magnetic resonance spectroscopy. The effects on proteoglycan of enzyme systems believed capable of acting in inflammatory arthritis and osteoarthritis are also under investigation. These studies will provide new information as to the structure and organization of proteoglycan in normal cartilage and help to clarify the nature and pathogenesis of the alterations occurring in arthritis. BIBLIOGRAPHIC REFERENCES: Keiser, H., Greenwald, R. A., Feinstein, G. and Janoff, A.: Degradation of Cartilage Proteoglycan by Human Leukocyte Granule Neutral Proteases -- A Model of Joint Injury. II. Degradation of Isolated Bovine Nasal Cartilage Proteoglycan. J. Clin. Invest. 57, 625 (1976). Sapolsky, A. I., Keiser, H., Howell, D. S. and Woessner, J. F. Jr.: Metalloproteases of Human Articular Cartilage that Digest Cartilage Proteoglycan at Neutral and Acid pH. J. Clin. Invest. 58, 1030 (1976).